Muders

BACKGROUND: To validate pulmonary computed tomography (CT) perfusion in a porcine model by invasive monitoring of cardiac output (CO) using thermodilution method. METHODS: Animals were studied at a single center, using a Swan-Ganz catheter for invasive CO monitoring as a reference. Fifteen pigs were included. Contrast-enhanced CT perfusion of the descending aorta and right and left pulmonary artery was performed. For variation purposes, a balloon catheter was inserted to block the contralateral pulmonary vascular bed; additionally, two increased CO settings were created by intravenous administration of catecholamines...

INTRODUCTION: Seizures are a common symptom of supratentorial meningiomas with pre- and postoperative seizure rates of approximately 30% and 12%, respectively, especially in parasagittal and convexity meningiomas. Less is known about the association between seizures and posterior fossa meningiomas. This study evaluates the prevalence, potential causes, and outcomes of seizures in patients who have undergone surgery for posterior fossa meningioma. METHODS: This is a retrospective, observational, single-center study of consecutive patients who underwent surgical resection of posterior fossa meningiomas between 2009 and 2017...

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential...

No abstract text is available yet for this article.

Neuropilin-2 (NRP2) is a cell surface receptor that plays key roles in lymphangiogenesis, but also in pathophysiological conditions such as cancer and inflammation. NRP2 targeting by efzofitimod, a novel immunomodulatory molecule, is currently being tested for the treatment of pulmonary sarcoidosis. To date, no anti-NRP2 antibodies are available for companion diagnostics. Here we describe the development and characterization of a novel NRP2 antibody. Using a variety of research techniques, that is, enzyme-linked immunoassay, Western blot, biolayer interferometry, and immunohistochemistry, we demonstrate that our antibody detects all major NRP2 isoforms and does not cross-react with NRP1...

No abstract text is available yet for this article.

Genomic selection (GS) is used in many animal and plant breeding programs to enhance genetic gain for complex traits. However, its optimal integration in clone breeding programs, for example potato, that up to now relied on phenotypic selection (PS) requires further research. In this study, we performed computer simulations based on an empirical genomic dataset of tetraploid potato to (i) investigate under a fixed budget how the weight of GS relative to PS, the stage of implementing GS, the correlation between an auxiliary trait and the target trait, the variance components, and the prediction accuracy affect the genetic gain of the target trait, (ii) determine the optimal allocation of resources maximizing the genetic gain of the target trait, and (iii) make recommendations to breeders how to implement GS in clone and especially potato breeding programs...

Monitoring regional blood flow distribution in the lungs appears to be useful for individually optimizing ventilation therapy. Electrical impedance tomography (EIT) can be used at the bedside for indicator-based regional lung perfusion measurement. Hypertonic saline is widely used as a contrast agent but could be problematic for clinical use due to potential side effects. In five ventilated healthy pigs, we investigated the suitability of five different injectable and clinically approved solutions as contrast agents for EIT-based lung perfusion measurement...

Efzofitimod is a first-in-class biologic based on a naturally occurring splice variant of histidyl-tRNA synthetase (HARS) that downregulates immune responses via selective modulation of neuropilin-2 (NRP2). Preclinical data found high expression of NRP2 in sarcoidosis granulomas. Treatment with efzofitimod reduced the granulomatous inflammation induced by P. acnes in an animal model of sarcoidosis. A dose escalating trial of efzofitimod in sarcoidosis with chronic symptomatic pulmonary disease found that treatment with efzofitimod was associated with improved quality of life with a trend towards reduced glucocorticoid use and stable to improved pulmonary function...

Despite remarkable advances in treating patients with metastatic melanoma, management of melanoma brain metastases remains challenging. Recent evidence suggests that epigenetic reprogramming is an important mechanism for the adaptation of melanoma cells to the brain environment. In this study, methylomes and transcriptomes of a cohort of matched melanoma metastases were evaluated by integrated omics data analysis. The identified 38 candidate genes displayed distinct promoter methylation and corresponding gene expression changes in intracranial compared to extracranial metastases...

This article was updated on January 18, 2023, because of a previous error, which was discovered after the preliminary version of the article was posted online. On page 103, in the first column of Table III, the continuous outcomes, which had been given as "Median" and "(range)", are now given as "Mean" and "(95% CI)", respectively.

BACKGROUND/AIM: The aim of this study was to analyze the predictive and prognostic value of the peritoneal cancer index (PCI) with regard to complete cytoreduction and clinical outcomes in patients with high-grade serous ovarian cancer. PATIENTS AND METHODS: In a cohort comprising 188 patients with high-grade serous ovarian cancer, the PCI was retrospectively assessed. Clinical factors and perioperative complications were analyzed according to different PCI groups...

Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development of PNI, tumor cells closely interact with the nerve components in the tumor microenvironment and create the perineural niche, which provides a supportive surrounding for their survival and invasion and benefits the nerve cells. Various transcription factors, cytokines, chemokines, and their related signaling pathways have been reported to be important in the progress of PNI...

Neuroendocrine (NE)-like tumors secrete various signaling molecules to establish paracrine communication within the tumor milieu and to create a therapy-resistant environment. It is important to identify molecular mediators that regulate this secretory phenotype in NE-like cancer. The current study highlights the importance of a cell surface molecule, Neuropilin-2 (NRP2), for the secretory function of NE-like prostate cancer (PCa). Our analysis on different patient cohorts suggests that NRP2 is high in NE-like PCa...

Importance: Although LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority) physicians experience bias in the workplace, there is a paucity of data on the experiences of physicians who identify specifically as transgender and/or gender expansive (TGE; gender expansive is an umbrella term encompassing individuals and gender identities that may exist beyond the binary framework [eg, may include nonbinary, genderqueer, and agender individuals]). Objectives: To explore the professional experiences of TGE physicians, identify barriers to inclusion, and highlight stakeholder-derived strategies that promote an inclusive workplace...

Aberrant transcriptional activity of androgen receptor (AR) is one of the dominant mechanisms for developing of castration-resistant prostate cancer (CRPC). Analyzing AR-transcriptional complex related to CRPC is therefore important towards understanding the mechanism of therapy resistance. While studying its mechanism, we observed that a transmembrane protein called neuropilin-2 (NRP2) plays a contributory role in forming a novel AR-transcriptional complex containing nuclear pore proteins. Using immunogold electron microscopy, high-resolution confocal microscopy, chromatin immunoprecipitation, proteomics, and other biochemical techniques, we delineated the molecular mechanism of how a specific splice variant of NRP2 becomes sumoylated upon ligand stimulation and translocates to the inner nuclear membrane...

The treatment of advanced renal cell carcinoma remains a challenge. To develop novel therapeutic approaches, primary cell cultures as an in vitro model are considered more representative than commercial cell lines. In this study, we analyzed the gene expression of previously established primary cell cultures of clear cell renal cell carcinoma by bulk (3'm)RNA sequencing and compared it to the tissue of origin. The objectives were the identification of dysregulated pathways under cell culture conditions. Furthermore, we assessed the suitability of primary cell cultures for studying crucial biological pathways, including hypoxia, growth receptor signaling and immune evasion...

BACKGROUND: Reconstruction of an osteoarthritic distal radioulnar joint (DRUJ) in patients with high physical demands and a long lifetime expectancy is challenging. A variety of methods like implant surgery and salvage procedures as partial or total ulnar head resection and the Sauve-Kapandji procedure are reasonable options in the elderly patient but not in young individuals since it often compromises manual power and stability and may cause impingement problems. Reconstruction of the DRUJ with rib perichondrium is a new treatment option with promising short-term outcome...

Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome (ARDS) is used to achieve oxygenation and protect lung ventilation. Near infrared spectroscopy (NIRS) measures cerebral regional tissue oxygenation (rSO 2 ) and may contribute to patient safety during interhospital transport under ECMO support. We evaluated 16 adult ARDS patients undergoing interhospital ECMO transport by measuring cerebral rSO 2 before and after initiation of ECMO support and continuously during transport. To compare peripheral oxygen saturation (SpO 2 ) measurement with rSO 2 , both parameters were analyzed...

Background : Electrical Impedance Tomography (EIT) is a radiation-free technique for image reconstruction. However, as the inverse problem of EIT is non-linear and ill-posed, the reconstruction of sharp conductivity images poses a major problem. With the emergence of artificial neural networks (ANN), their application in EIT has recently gained interest. Methodology : We propose an ANN that can solve the inverse problem without the presence of a reference voltage. At the end of the ANN, we reused the dense layers multiple times, considering that the EIT exhibits rotational symmetries in a circular domain...